Hospital pharmacist interventions for the management of oral mucositis in patients with head and neck cancer receiving chemoradiotherapy: a multicenter, prospective cohort study.

PURPOSE: Oral mucositis is a severe adverse event in patients with head and neck cancer (HNC) receiving chemotherapy and radiotherapy that may cause the termination of cancer treatment. In this study, we aimed to reveal the benefits of pharmacist interventions in oral health care for patients with HNC receiving concurrent chemoradiotherapy (CCRT). METHODS: We conducted a multicenter, prospective cohort study on 173 patients from September 2019 to August 2022. We evaluated the association between the occurrence of oral mucositis during CCRT and various factors in the absence or presence of direct medication instructions from hospital pharmacists. RESULTS: Sixty-eight patients received medication instructions from pharmacists (the pharmacist intervention group), whereas 105 patients did not receive instructions (the control group). Logistic regression analysis showed that grade 2 (Gr 2) oral mucositis was significantly lower in patients receiving pharmacist interventions than in patients in the control group (adjusted odds ratio [aOR], 0.42; 95% confidence interval [CI], 0.18-0.96; P = 0.04). The time to onset of Gr 2 oral mucositis was significantly longer in the pharmacist intervention group than in the control group (hazard ratio, 0.53; 95% CI, 0.29-0.97; P = 0.04). CONCLUSION: Direct intervention, especially when provided by hospital pharmacists, can have a real effect in supporting patients with HNC experiencing severe side effects of treatments. Moreover, the integration of pharmacists into the oral healthcare team is becoming even more essential to reduce the severity of side effects.

[Effects of Serum Sodium Concentrations on Nausea and Vomiting after Moderately Emetogenic Chemotherapy].

Chemotherapy-induced nausea and vomiting (CINV) is the most unbearable adverse effect of chemotherapy. The antiemesis guidelines of the National Comprehensive Cancer Network indicate that hyponatremia is a risk factor for CINV, although the relationship between the incidence of CINV and hyponatremia has not been sufficiently studied. This two-center prospective observational study evaluated whether low serum sodium concentrations were a risk factor for CINV. The study included 34 patients who were scheduled to receive first-line carboplatin- or oxaliplatin-based chemotherapy for gynecological or colorectal cancers. Patient diaries were used to record the daily incidences of CINV events during a 5-day period. The patients were divided based on the median serum sodium concentration into a low Na+ group (<141 mEq/L) and a high Na+ group (≥141 mEq/L). The incidences of delayed nausea were 27.8% in the high Na+ group and 62.5% in the low Na+ group (p=0.042), with complete control rates (no vomiting, rescue medication, or grade 2 nausea) of 77.8% and 43.8%, respectively (p=0.042). The time to complete control failure in each group was analyzed using the Kaplan-Meier method, which revealed a significantly shorter time in the low Na+ group (p=0.03). Therefore, these results indicate that low serum sodium concentrations may increase the risk of CINV.

Electronic effects of para-substitution on acetophenones in the reaction of rat liver 3alpha-hydroxysteroid dehydrogenase.

Stereoselective reductive metabolism of various p-substituted acetophenone derivatives was studied using isolated rat liver 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD). Kinetic experiments were performed and analyzed by measuring the products by HPLC using a chiral column. The results demonstrated that the presence of an electron-withdrawing substituent on the benzene ring plays an important role in determining the reduction rate in the syntheses of various (S)-alcohols from their corresponding carbonyl compounds. A plot of log {(V(max)/K(m))X/(V(max)/K(m))H} versus the substituent parameter (pi, sigma(para), Es) shows an increasing rate mainly for electron-withdrawing substituents, with a correlation coefficient (r(2)) of 0.97 which was obtained for triplicate data that were significant at the p<0.0001 level. With this in mind, new drugs can be designed that exploit this reduction pathway by introducing an electron-withdrawing group adjacent to the reduction site when a reduction reaction is desired, or by adding an electron-donating group when minimization of the reduction pathway is desired.

Nocturnal oxygen therapy prevents progress of congestive heart failure with central sleep apnea.

BACKGROUND: Sleep disordered breathing has been reported to be associated with congestive heart failure (CHF). Nocturnal oxygen has been shown to abolish apnea. The aim of this study is to examine whether nocturnal oxygen reduces sympathetic nerve activity, and prevents progress of CHF. METHODS: 93 patients with left ventricular ejection fractions < 60%, were examined with overnight saturation monitoring for an oxygen desaturation index. Subjects with oxygen desaturation of 4% > or = 4/h were examined with polysomnography. Apnea-hypopnea index (AHI) was calculated as the total number of episodes of apnea and hypopnea per hour of sleep. We started nocturnal oxygen for the patients with AHI > or = 20. Urinary and plasma catecholamines concentrations, serum brain natriuretic peptide, human atrial natriuretic peptide, and endothelial nitric oxide synthase levels were measured before and after starting oxygen. RESULTS: Compared among the three groups, CHF with central sleep apnea (CHF-CSA) group had significantly higher 24-h urinary adrenaline (CHF-CSA: 4.411+/-2.940 micromol/day, CHF with obstructive sleep apnea (CHF-OSA): 2.686+/-1.084 micromol/day, CHF without apnea (CHF-N): 3.178+/-1.778 micromol/day, P<0.05). Oxygen therapy significantly decreased AHI and 4 serum BNP levels (from 91.75+/-80.35 pg/ml to 52.75+/-45.70 pg/ml, mean change=33.85 pg/ml, P=0.0208). Serum eNOS levels were lower in CHF-CSA group and CHF-OSA group than in CHF-N group (CHF-CSA: 15.89+/-10.75 pg/ml, CHF-OSA: 7.46+/-3.91 pg/ml, CHF-N: 27.33+/-14.83 pg/ml, P<0.05). CONCLUSIONS: Nocturnal oxygen may prevent progress of CHF with central sleep apnea.

Purification and characterization of rat liver enzyme catalyzing stereoselective reduction of acetylpyridines.

Acetylpyridines (1-3) are known as aroma components of foods, perfumes, and smoking suppressants, showing several biological activities and constituting part of the structure of some important biologically active compounds. We purified and characterized an enzyme that catalyzes the stereoselective reduction of acetylpyridines so that we could clarify its function. The enzyme participating in the reductive metabolism of 4-acetylpyridine (1) in the rat liver was purified by successively applying ammonium sulfate fractionation, anion-exchange, gel filtration, and affinity chromatography, and it was definitively identified as 3alpha-HSD. It preferentially reduced acetylpyridines (1-3) and acetophenone (7) to their corresponding (S)-alcohols, with high enantioselectivity. Kinetic analyses of the compounds were performed, and the V(max)/K(m) values decreased in the order of 4-, 2-, and 3-acetylpyridine (1, 3, 2), while acetophenone (7) showed almost the same value as 3-acetylpyridine (2). These results suggested that the reduction of the substrates by 3alpha-HSD is affected by the nitrogen atom in the aromatic ring.

Overexpression of mitochondrial genes is caused by interactions between the nucleus of Brassica rapa and the cytoplasm of Diplotaxis muralis in the leaves of alloplasmic lines of B. rapa.

In Brassica species, alloplasmic lines displaying cytoplasmic male sterility (CMS) are established by combining the nucleus from B. rapa with the cytoplasm from Diplotaxis muralis. The failure to observe restriction fragment length polymorphism (RFLP) patterns of mitochondrial genes ( coxII, coxIII, atpA, atp6, atp9, cob, nad3, nad6, and nad9) between alloplasmic lines of B. rapa and D. muralis indicates that introgression of the B. rapa nucleus into the cytoplasm of D. muralis does not cause any alterations in the structure of the mitochondrial genome. To investigate how the nucleus influences the cytoplasm, we examined the expression of mitochondrial genes in the leaves of euplasmic and alloplasmic lines of B. rapa and D. muralis. We detected higher levels of mitochondrial gene mRNAs in alloplasmic lines of B. rapa than in D. muralis. Patterns of mitochondrial gene transcription also differed among the alloplasmic lines of B. rapa. Thus, expression of mitochondrial genes in alloplasmic lines of B. rapa differed in the leaves compared to D. muralis. Overexpression of mitochondrial genes may be the result of novel interactions between the nucleus and the mitochondria in alloplasmic lines of B. rapa. Further study is necessary to clarify how these phenomena are involved in CMS.